基于网络药理学研究红花抗心肌缺血的作用机制

Study on the Mechanism of Carthamus tinctorius in Treatment of Myocardial Ischemia Based on Network Pharmacology

目的:构建红花药材-成分-靶点-通路网络,探讨红花治疗心肌缺血的作用机制。方法:以红花中符合口服生物利用度(OB)≥30%、类药性(DL)≥0.18的化合物作为研究对象,通过中药系统药理学数据库与分析平台(TCMSP)对进行检索并得到靶点,并在UniProt数据库靶点检索基因名,通过GeneCards数据库对心肌缺血进行检索,得到心肌缺血靶点。将心肌缺血与红花靶点取交集。将所得到交集靶点进行蛋白质-蛋白质相互作用(PPI)分析、基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。利用Cytoscape 3.8.0软件绘制药材-化合物-靶点-通路网络图。结果:得到红花16个活性成分,192个靶点,在GeneCards数据库搜索并筛选得到335个心肌缺血靶点。得到红花靶点与心肌缺血交集靶点58个。交集靶点PPI度值排名前3位为IL6、TNF、VEGFA。GO与KEGG通路富集分析分别选取前5个条目绘制气泡图。药材-化合物-靶点-通路网络中有89个节点,338条边。节点前三的化合物为:槲皮素、山柰酚与木犀草素。结论:红花可能通过多种化学成分、多靶点与多途径起到治疗心肌缺血的作用,为其在临床使用提供理论依据。

Objective:To construct Carthamus tinctorius medicinal material composition-target-pathway network and to explore the mechanism of Carthamus tinctorius in the treatment of myocardial ischemia.Methods:The compounds in Carthamus tinctorius which met OB≥30%,DL≥0.18 were taken as the research objects.The components and targets which met the requirements were searched by TCMSP Database,and the gene names of the targets were searched in UniProt Database.The myocardial ischemia targets were obtained by searching for myocardial ischemia in GeneCards Database.The intersection of myocardial ischemia target and Carthamus tinctorius target was obtained.The intersection targets were analyzed by PPI and GO and KEGG pathways.Cytoscape 3.8.0 software was used to draw the network diagram of medicinal drug-compound-target-pathway.Results:There were 16 active compounds and 192 targets in Carthamus tinctorius,and 335 targets of myocardial ischemia were obtained by searching for myocardial ischemia in GeneCards.Taking Carthamus tinctorius target and myocardial ischemia target as intersection,58 intersection targets were obtained.PPI analysis was performed on the intersection targets,and the top 3 targets with PPI score were:IL6,TNF,and VEGFA.The enrichment analysis of GO and KEGG pathways selected the first 5 entries to draw bubble charts.There were 89 nodes and 338 edges in the medicinal material-compound-target-pathway network.The top 3 compounds at the node were:quercetin,kaempferol and luteolin.Conclusion:Carthamus tinctorius may play a role in the treatment of myocardial ischemia through various chemical components,multiple targets and multiple ways,which provides theoretical basis for its clinical use.